Use of Nitrous Oxide for Pain and Anxiety Management During Cervical Cerclage Removal

April 2, 2026 updated by: Gil Friedman, Kaplan Medical Center

Use of Nitrous Oxide for Pain and Anxiety Management During Cervical Cerclage Removal- A Multicenter Randomized Controlled Study

The goal of this clinical trial is to determine whether inhaled nitrous oxide can reduce pain and anxiety during cervical cerclage removal compared with standard care. Cervical cerclage removal is commonly performed in the outpatient setting during the third trimester of pregnancy and may be associated with discomfort and anxiety despite being a brief procedure.

The study will include pregnant women aged 18 years or older undergoing elective cervical cerclage removal at 36 weeks of gestation or later.

The main questions the study aims to answer are:

  • Does inhaled nitrous oxide reduce pain during cervical cerclage removal?
  • Does inhaled nitrous oxide reduce anxiety during the procedure?
  • Does the use of nitrous oxide improve overall patient satisfaction during cerclage removal?

Researchers will compare women receiving inhaled nitrous oxide to those receiving standard care without analgesia, as routinely practiced in the participating institutions, in order to determine whether nitrous oxide improves pain control and patient experience during the procedure.

Participants will:

  • Be randomly assigned to receive either inhaled nitrous oxide (50% nitrous oxide / 50% oxygen) or standard care without analgesic treatment during cervical cerclage removal.
  • Undergo the procedure according to routine clinical practice in the participating centers.
  • Complete questionnaires assessing pain and anxiety, including a visual analog scale (VAS) for pain and the State-Trait Anxiety Inventory (STAI).
  • Have routine clinical data recorded from their medical records, including maternal vital signs and any procedure-related side effects.

Study Overview

Status

Not yet recruiting

Conditions

Intervention / Treatment

Detailed Description

Cervical insufficiency is a recognized risk factor for spontaneous preterm birth, which remains a major cause of perinatal morbidity and mortality worldwide. Cervical cerclage is an established intervention used in carefully selected patients to reduce the risk of preterm birth.

While cerclage placement is typically performed under anesthesia in the operating room, cerclage removal is usually carried out in the outpatient setting during the late third trimester of pregnancy. Despite being a brief procedure, many patients experience pain, discomfort, and anxiety during cerclage removal. Evidence regarding optimal pain management strategies for this procedure remains limited, and most patients currently undergo cerclage removal without analgesia.

Nitrous oxide (N₂O) is an inhaled gas with well-established analgesic and anxiolytic properties. It has a rapid onset and offset of action and a favorable safety profile. Nitrous oxide is widely used in obstetrics, particularly for labor analgesia, and has also been used for pain management during minor medical procedures. However, its use specifically for cervical cerclage removal has not been well studied.

This study is a multicenter randomized controlled trial designed to evaluate whether inhaled nitrous oxide reduces pain and anxiety during elective cervical cerclage removal. Participants will be randomly assigned in a 1:1 ratio to receive either inhaled nitrous oxide (50% nitrous oxide / 50% oxygen) during the procedure or standard care without analgesic treatment, as routinely practiced in the participating institutions. Randomization will be stratified by site and implemented using sequentially numbered sealed envelopes opened immediately prior to the procedure.

All procedures will be performed according to routine clinical practice in the participating centers. Maternal and procedural data will be collected from medical records, including procedure duration, maternal vital signs, and any reported side effects such as nausea, dizziness, or headache. Pain intensity will be assessed using a 0-100 mm visual analog scale (VAS), and anxiety levels will be evaluated using the State-Trait Anxiety Inventory (STAI). Additional outcomes will include maternal heart rate during the procedure and patient satisfaction with the procedure.

This trial aims to determine whether inhaled nitrous oxide can effectively reduce pain and anxiety during cervical cerclage removal. The findings of this study may provide evidence to support improved pain management strategies for this procedure and may contribute to enhancing patient experience during cerclage removal.

Study Type

Interventional

Enrollment (Estimated)

60

Phase

  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Locations

  • Israel
      • Holon, Israel
        • Edith Wolfson Medical Center
        • Contact:
      • Kfar Saba, Israel
        • Meir Medical Center
        • Contact:
      • Petah Tikva, Israel
        • Rabin Medical Center
        • Contact:
          • Bar Narkis
          • Phone Number: +972546335114
    • Central District
      • Rehovot, Central District, Israel, 7639302

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  • Age ≥18 years
  • Women at ≥34 weeks of gestation
  • Singleton or twin pregnancy
  • Ability to understand, sign informed consent, and complete questionnaires

Exclusion Criteria:

  • Triplet or higher-order pregnancy
  • Contraindications to nitrous oxide use
  • Fetal monitoring category 2 or higher
  • Maternal body temperature >38°C
  • Significant vaginal bleeding
  • Severe preeclampsia
  • Cerclage removal under general anesthesia
  • Language or cognitive barrier
  • Baseline pain >3 on VAS scale, prior to the procedure

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Inhaled Nitrous Oxide During Cervical Cerclage Removal

Participants in this arm will receive inhaled nitrous oxide (50% nitrous oxide / 50% oxygen) administered via a demand-valve mask during cervical cerclage removal. The system includes a one-way valve and is self-administered by the patient, who holds the mask and inhales as needed. The equipment is identical to the device routinely used for labor analgesia in the participating institutions and will be operated and monitored by trained midwives experienced in nitrous oxide administration.

Continuous pulse oximetry monitoring will be initiated prior to gas administration. Nitrous oxide inhalation will begin following instruction from the performing physician, and the procedure will start approximately three minutes after inhalation begins once adequate analgesia and anxiolysis are achieved. After completion of the procedure, nitrous oxide will be discontinued and the patient will breathe room air. The patient will remain in bed for approximately 15 minutes with fetal monitoring to conf
Drug: Inhaled nitrous oxide

Inhaled nitrous oxide (50% nitrous oxide / 50% oxygen) administered via a demand-valve mask during cervical cerclage removal. The system includes a one-way valve and is self-administered by the patient, who holds the mask and inhales as needed. The device is identical to the equipment routinely used for labor analgesia in the participating institutions and is operated and monitored by trained midwives experienced in nitrous oxide administration.

Nitrous oxide inhalation begins following instruction from the performing physician. The procedure starts approximately three minutes after inhalation begins, once adequate analgesia and anxiolysis are achieved. Continuous pulse oximetry monitoring is performed during administration. After completion of the procedure, nitrous oxide is discontinued and the patient breathes room air.

Other Names:
  • N2O
No Intervention: Standard Care Without Analgesia
Participants in this arm will undergo cervical cerclage removal without analgesia, in accordance with the standard practice across the participating institutions. The procedure will be performed in the outpatient setting following routine clinical protocols. Maternal vital signs and fetal status will be monitored according to standard clinical practice. No nitrous oxide or other analgesic intervention will be administered as part of the study protocol.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Pain intensity during cervical cerclage removal
Time Frame: 3-5 minutes following completion of the procedure
Pain intensity will be assessed using a 0-100 mm visual analog scale (VAS). Participants will rate the level of pain experienced during the procedure 3-5 minutes after completion of the cerclage removal.
3-5 minutes following completion of the procedure

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Procedure duration
Time Frame: During procedure
Total duration of the cerclage removal procedure, measured in minutes from the beginning of the procedure to completion.
During procedure
Change in maternal heart rate during procedure
Time Frame: Baseline measurement prior to the procedure and continuous monitoring during the procedure
Difference (delta) between baseline maternal heart rate and the maximal heart rate recorded during the procedure
Baseline measurement prior to the procedure and continuous monitoring during the procedure
Adverse events
Time Frame: During procedure
Occurrence of adverse events including nausea, dizziness, headache, or dyspnea reported during or immediately after the procedure
During procedure
Conversion to neuraxial or general anesthesia
Time Frame: During the procedure
Need to convert from the assigned study condition (nitrous oxide or no analgesia) to epidural, spinal, or general anesthesia due to inability to complete the procedure
During the procedure
Difference between expected pain and experienced pain
Time Frame: Baseline (prior to procedure) and 3-5 minutes following completion of the procedure
Expected and experienced pain will be assessed using a 0-100 mm Visual Analog Scale (VAS), where higher scores indicate greater pain intensity. The difference between expected and experienced pain scores will be calculated.
Baseline (prior to procedure) and 3-5 minutes following completion of the procedure
Change in anxiety level (STAI)
Time Frame: Baseline (before procedure) and 3-5 minutes after completion of the procedure
Anxiety levels will be assessed using the State-Trait Anxiety Inventory (STAI). The STAI score ranges from 20 to 80, with higher scores indicating higher levels of anxiety. Participants will complete the questionnaire before the procedure and again after cerclage removal. The change in STAI score will be analyzed.
Baseline (before procedure) and 3-5 minutes after completion of the procedure
Patient satisfaction
Time Frame: 3-5 minutes after completion of the procedure
Patient satisfaction will be assessed using a 5-point Likert scale, where 1 indicates very low satisfaction and 5 indicates very high satisfaction. The questionnaire will be completed after cerclage removal.
3-5 minutes after completion of the procedure
Physician-rated procedural difficulty
Time Frame: 3-5 minutes following completion of the procedure
The performing physician will provide a subjective assessment of the technical difficulty of cervical cerclage removal. Procedural difficulty will be assessed using a 5-point Likert scale, where 1 indicates very easy and 5 indicates very difficult.
3-5 minutes following completion of the procedure

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Kaplan Medical Center

Collaborators

Rabin Medical Center
Meir Medical Center
Wolfson Medical Center
Clalit Health Services

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Estimated)

May 1, 2026

Primary Completion (Estimated)

May 1, 2028

Study Completion (Estimated)

May 1, 2028

Study Registration Dates

First Submitted

March 18, 2026

First Submitted That Met QC Criteria

March 18, 2026

First Posted (Actual)

March 25, 2026

Study Record Updates

Last Update Posted (Actual)

April 8, 2026

Last Update Submitted That Met QC Criteria

April 2, 2026

Last Verified

March 1, 2026

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 0034-26-KMC1-C

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

UNDECIDED

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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